An understanding of the mechanisms of aging is dependent upon a knowledge of the structural and functional changes which occur as a result of aging. Unfortunately, little is known about such changes. Of the many clinically observable changes associated with age in skin it is important to distinguish those which are intrinsic or "physiologic" from those which are the result of an accumulation of environmental insults. In makine this distinction it is useful to examine age changes in oral mucosa which is exposed to a different environment from that of the skin and thus provides an excellent tissue for comparison. The major aim of the study is to determine the differences with age in structure and function of the skin of the ear, back and footpad and oral mucosa from the palate, cheek and tongue of young (12-16 weeks), and old (90-94 weeks) C57 BL/6 mice. Studies of the influence of age on skin and oral mucosa will involve examination of 1) proliferative activity both in vivo and in vitro and turnover of nucleated cell and deratin squame compartment using autoradiography; 2) epithelial architecture, thickness and frequency of specialized units such as sebaceous glands and tongue papilae; 3) numerical density of epithelial Langerhans cells; 4) metabolic activities associated with epithelial proliferation and keratinization; 5) relative densities and proportions of the connective tissue components as determined by the techniques of ultrastructural stereology; 6) the reaction of the tissues as a whole to hyperplasiogenic agents and exisional wounding as judged by cell proliferation, ultrastructural stereology and metabolic activity. The objective of the proposed project is to determine, in an inimal model, which fundamental properties of skin and oral mucosa might be age related. Such identification could ultimately lead to a better understanding of the aging process and its influence on dermatologic disease in the elderly.